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<p>Pancreatic ductal adenocarcinoma (PDAC) is ranked by the lowest 5-year survival rate worldwide. Given the lack of early symptoms and diagnostic biomarkers, most patients present with either local or distant metastasis at diagnosis. We previously demonstrated that Galectin-3-binding protein (Gal-3BP) is overexpressed in PDAC cells and promotes metastasis through the EGFR pathway, using proteomic analysis of PDAC tumor interstitial fluid (TIF). In the present study, we show the Gal-3BP promotes angiogenesis in PDAC by vascular endothelial growth factor A (VEGFA) upregulation via STAT3 activation. Furthermore, we reveal the Gal-3BP directly promotes migration and tube formation of vascular endothelial cells through STAT3 phosphorylation, mediated not by a VEGF receptor but by VAMP5. To explore the clinical application of these findings, we developed a humanized, high-affinity Gal-3BP antibody to block the dual angiogenic function of Gal-3BP. The #132 clone of the Gal-3BP antibody significantly reduced blood vessel density in PDAC orthotopic tumors and attenuated PDAC metastasis in a lung metastasis model. Therefore, we demonstrate the antibody-mediated blockade of Gal-3BP attenuates the angiogenesis in PDAC and propose it as a novel therapeutic strategy.</p>

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The Galectin-3-binding protein promotes angiogenesis in pancreatic cancer via simultaneous upregulation of VEGFA and direct HUVEC activation mediated by and VAMP5-STAT3

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月18日

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  • Ye Jin Lim,
  • Dong Woo Son,
  • Eun Ji Lee,
  • Chae Won Yu,
  • Yun Ok Oh,
  • Min Jung Cha,
  • Hyori Kim,
  • Kyunggon Kim,
  • Suhwan Chang

摘要

Pancreatic ductal adenocarcinoma (PDAC) is ranked by the lowest 5-year survival rate worldwide. Given the lack of early symptoms and diagnostic biomarkers, most patients present with either local or distant metastasis at diagnosis. We previously demonstrated that Galectin-3-binding protein (Gal-3BP) is overexpressed in PDAC cells and promotes metastasis through the EGFR pathway, using proteomic analysis of PDAC tumor interstitial fluid (TIF). In the present study, we show the Gal-3BP promotes angiogenesis in PDAC by vascular endothelial growth factor A (VEGFA) upregulation via STAT3 activation. Furthermore, we reveal the Gal-3BP directly promotes migration and tube formation of vascular endothelial cells through STAT3 phosphorylation, mediated not by a VEGF receptor but by VAMP5. To explore the clinical application of these findings, we developed a humanized, high-affinity Gal-3BP antibody to block the dual angiogenic function of Gal-3BP. The #132 clone of the Gal-3BP antibody significantly reduced blood vessel density in PDAC orthotopic tumors and attenuated PDAC metastasis in a lung metastasis model. Therefore, we demonstrate the antibody-mediated blockade of Gal-3BP attenuates the angiogenesis in PDAC and propose it as a novel therapeutic strategy.